IDENTIFICATION OF NOVEL SELECTIVE ANTAGONISTS FOR BESTROPHIN-1 PROTEIN BY HOMOLOGY MODELING AND MOLECULAR DOCKING Research Article
Priya Rajendra Rao · 2012
Bestrophin-1 (BEST1), also known as VMD2 belongs to the bestrophin gene family. It codes for a protein that may act as a channel to control the movement of negatively charged chloride ions into or out of cells in the retina or may regulate voltage-gated L-type calcium-ion channels. Thus the mutation in this gene leads to progressive vision loss known as Best Vitelliform macular dystrophy. It is inherited in an autosomal dominant manner. Hence, Bestrophin-1 is an important constituent of this disease which is chosen for structure prediction using homology modeling, with the aid of software called insight II. The 3D structure is predicted and the final model is refined by energy minimization. The quality of the refined model is assessed using PROCHECK. The interaction between the predicted structure of Bestrophin-1 and its potential inhibitors namely Verteporfin, Fluorescein, L- Cystine and Fluocinolone Acetonide is analyzed by in silico method with the help of Autodock. The results indicate that certain residues like ARG 82, ARG 84 and HIS 197 are highly conserved across the active site stretches of bestrophin-1 and the inhibitor Verteporfin gives best interaction in this active site than other compounds. This study provides an insight into the structure of bestrophin-1 and also gives an idea about potential sites responsible for inhibitory action that could further be substantiated by experimental investigations.